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Effect of calcineurin inhibitors on low-density lipoprotein oxidation.

Abstract

INTRODUCTION

Low-density lipoprotein (LDL) oxidation is considered a key factor in the biological processes that trigger and accelerate atherosclerosis. Reported data suggest that tacrolimus improves the lipid profile in renal transplant recipients.

OBJECTIVE

The objective of this study was to analyze the effect of converting from cyclosporine to tacrolimus on lipoprotein oxidation in renal transplant recipients.

METHODS

We studied a group of 12 recipients (6 men and 6 women of mean age 55 +/- 11 years) treated with a cyclosporine-mycophenolate mofetil (MMF)-prednisone combination that was converted to tacrolimus-MMF-prednisone because of gingival hyperplasia. The LDL fraction was isolated by density-gradient ultracentrifugation. Oxidative stress was studied before converting (baseline) and at 6 and 12 weeks, thereafter by in vivo oxidation analysis of LDL, a direct assay of oxidized LDL (oxLDL) and oxLDL autoantibodies (Ab-oxLDL) using enzyme-immunoassay techniques. We measured total cholesterol (TC), triglyceride, LDL-cholesterol, high-density lipoprotein (HDL)-cholesterol, ApoA1, ApoB, and Lp(a) levels.

RESULTS

The change to tacrolimus resulted in significant decreases in TC levels, 213 +/- 30 (B) versus 185 +/- 27 (12s) (P < .01); LDL, 129 +/- 24 (B) versus 104 +/- 14 (12s) (P = .002); and ApoB 98 +/- 15 (B) versus 85 +/- 10 (12s) (P < .01). HDL levels significantly increased (45 +/- 10 vs 48 +/- 10 [12s]; P = .018), whereas oxLDL concentrations decreased significantly after conversion (B) (55.42 +/- 10.61 vs 12s 45.76 +/- 10.21; P < .01). Converting to tacrolimus produced a nonsignificant decrease in Ab-oxLDL (baseline 204.88 +/- 134.49 vs 12s 179.51 +/- 143.54). A correlation was observed between LDL and oxLDL (r = 65, P = .02 [B] and r = 0.7, P = .01 [12s]) but not between oxLDL levels and Ab-oxLDL concentration (r = -0.05, P = .87 [3] and r = -0.1, P = .77 [12s]).

CONCLUSIONS

In renal transplantation, tacrolimus therapy was associated with a better lipid profile and lower in vivo LDL oxidation when compared with cyclosporine treatment.

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  • Authors+Show Affiliations

    ,

    Renal Transplant Unit, Hospital Clínic, Barcelona, Spain. fcofan@clinic.ub.es

    , , , ,

    Source

    Transplantation proceedings 37:9 2005 Nov pg 3791-3

    MeSH

    Adult
    Aged
    Analysis of Variance
    Calcineurin
    Cholesterol
    Creatinine
    Cyclosporine
    Drug Therapy, Combination
    Female
    Humans
    Immunosuppressive Agents
    Kidney Transplantation
    Lipoproteins, LDL
    Male
    Middle Aged
    Oxidation-Reduction
    Tacrolimus

    Pub Type(s)

    Clinical Trial
    Comparative Study
    Journal Article

    Language

    eng

    PubMed ID

    16386540

    Citation

    Cofan, F, et al. "Effect of Calcineurin Inhibitors On Low-density Lipoprotein Oxidation." Transplantation Proceedings, vol. 37, no. 9, 2005, pp. 3791-3.
    Cofan F, Cofan M, Campos B, et al. Effect of calcineurin inhibitors on low-density lipoprotein oxidation. Transplant Proc. 2005;37(9):3791-3.
    Cofan, F., Cofan, M., Campos, B., Guerra, R., Campistol, J. M., & Oppenheimer, F. (2005). Effect of calcineurin inhibitors on low-density lipoprotein oxidation. Transplantation Proceedings, 37(9), pp. 3791-3.
    Cofan F, et al. Effect of Calcineurin Inhibitors On Low-density Lipoprotein Oxidation. Transplant Proc. 2005;37(9):3791-3. PubMed PMID: 16386540.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Effect of calcineurin inhibitors on low-density lipoprotein oxidation. AU - Cofan,F, AU - Cofan,M, AU - Campos,B, AU - Guerra,R, AU - Campistol,J-M, AU - Oppenheimer,F, PY - 2006/1/3/pubmed PY - 2006/2/16/medline PY - 2006/1/3/entrez SP - 3791 EP - 3 JF - Transplantation proceedings JO - Transplant. Proc. VL - 37 IS - 9 N2 - INTRODUCTION: Low-density lipoprotein (LDL) oxidation is considered a key factor in the biological processes that trigger and accelerate atherosclerosis. Reported data suggest that tacrolimus improves the lipid profile in renal transplant recipients. OBJECTIVE: The objective of this study was to analyze the effect of converting from cyclosporine to tacrolimus on lipoprotein oxidation in renal transplant recipients. METHODS: We studied a group of 12 recipients (6 men and 6 women of mean age 55 +/- 11 years) treated with a cyclosporine-mycophenolate mofetil (MMF)-prednisone combination that was converted to tacrolimus-MMF-prednisone because of gingival hyperplasia. The LDL fraction was isolated by density-gradient ultracentrifugation. Oxidative stress was studied before converting (baseline) and at 6 and 12 weeks, thereafter by in vivo oxidation analysis of LDL, a direct assay of oxidized LDL (oxLDL) and oxLDL autoantibodies (Ab-oxLDL) using enzyme-immunoassay techniques. We measured total cholesterol (TC), triglyceride, LDL-cholesterol, high-density lipoprotein (HDL)-cholesterol, ApoA1, ApoB, and Lp(a) levels. RESULTS: The change to tacrolimus resulted in significant decreases in TC levels, 213 +/- 30 (B) versus 185 +/- 27 (12s) (P < .01); LDL, 129 +/- 24 (B) versus 104 +/- 14 (12s) (P = .002); and ApoB 98 +/- 15 (B) versus 85 +/- 10 (12s) (P < .01). HDL levels significantly increased (45 +/- 10 vs 48 +/- 10 [12s]; P = .018), whereas oxLDL concentrations decreased significantly after conversion (B) (55.42 +/- 10.61 vs 12s 45.76 +/- 10.21; P < .01). Converting to tacrolimus produced a nonsignificant decrease in Ab-oxLDL (baseline 204.88 +/- 134.49 vs 12s 179.51 +/- 143.54). A correlation was observed between LDL and oxLDL (r = 65, P = .02 [B] and r = 0.7, P = .01 [12s]) but not between oxLDL levels and Ab-oxLDL concentration (r = -0.05, P = .87 [3] and r = -0.1, P = .77 [12s]). CONCLUSIONS: In renal transplantation, tacrolimus therapy was associated with a better lipid profile and lower in vivo LDL oxidation when compared with cyclosporine treatment. SN - 0041-1345 UR - https://www.unboundmedicine.com/medline/citation/16386540/Effect_of_calcineurin_inhibitors_on_low_density_lipoprotein_oxidation_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0041-1345(05)01220-0 DB - PRIME DP - Unbound Medicine ER -